Insect vector-born diseases continue to be a major source of mortality worldwide. The continuous development of new tools to study and combat these diseases and the insects that transmit them is essential. The long term goals of this research program are to develop genetic engineering tools for insects of medical significance to man and to use these new tools to gain a better understanding of the basic biology of insect/pathogen and parasite interactions. These new tools will also be used to develop new genetics-based methods for interfering with insect vector-born disease transmission. This proposal has two principal components - continued development of the Hermes gene vector system to improve its efficiency and host range, and the development of genetic tools to investigate Culex mosquitoes. The specific aims are to 1) understand the modes of integration used by Hermesin mosquito and how these modes are regulated 2) determine the mechanisms, range and consequences of hAT element interactions in insects, 3) increase the recombination activity of Hermes transposase through protein modification and engineering, 4) develop gene vector and enhancer-trapping tools for Culex mosquitoes. 5) develop a functional anopheline hAT element-based gene vector system. These aims will be accomplished using genetic and molecular genetic methods.